Thalidomide protects mice against LPS-inducecl shock

Thalidomide has been shown to selectively inhibit TNF-α production in vitro by lipopolysaccharide (LPS)-stimulated monocytes. TNF-α has been shown to play a pivotal role in the pathophysiology of endotoxic shock. Using a mouse model of LPS-induced shock, we investigated the effects of thalidomide on the production of TNF-α and other cytokines and on animal survival. After injection of 100-350 μg LPS into mice, cytokines including TNF-α, IL-6, IL-10, IL-1ß, GM-CSF and IFN-γ were measured in the serum. Administration of 200 mg/kg thalidomide to mice before LPS challenge modified the profile of LPS-induced cytokine secretion. Serum TNF-α levels were reduced by 93%, in a dose-dependent manner, and TNF-α mRNA expression in the spleens of mice was reduced by 70%. Serum IL-6 levels were also inhibited by 50%. Thalidomide induced a two-fold increase in serum IL-10 levels. Thalidomide treatment did not interfere with the production of GM-CSF, IL-1ßor IFN-γ. The LD₅₀ of LPS in this model was increased by thalidomide pre-treatment from 150 μg to 300 μg in 72 h. Thus, at otherwise lethal doses of LPS, thalidomide treatment was found to protect animals from death.